{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:27:37Z","timestamp":1780540057541,"version":"3.54.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0907000"],"award-info":[{"award-number":["2020YFA0907000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Computational protein sequence design has been widely applied in rational protein engineering and increasing the design accuracy and efficiency is highly desired.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we present ProDESIGN-LE, an accurate and efficient approach to protein sequence design. ProDESIGN-LE adopts a concise but informative representation of the residue\u2019s local environment and trains a transformer to learn the correlation between local environment of residues and their amino acid types. For a target backbone structure, ProDESIGN-LE uses the transformer to assign an appropriate residue type for each position based on its local environment within this structure, eventually acquiring a designed sequence with all residues fitting well with their local environments. We applied ProDESIGN-LE to design sequences for 68 naturally occurring and 129 hallucinated proteins within 20\u2009s per protein on average. The designed proteins have their predicted structures perfectly resembling the target structures with a state-of-the-art average TM-score exceeding 0.80. We further experimentally validated ProDESIGN-LE by designing five sequences for an enzyme, chloramphenicol O-acetyltransferase type III (CAT III), and recombinantly expressing the proteins in Escherichia coli. Of these proteins, three exhibited excellent solubility, and one yielded monomeric species with circular dichroism spectra consistent with the natural CAT III protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code of ProDESIGN-LE is available at https:\/\/github.com\/bigict\/ProDESIGN-LE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad122","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T08:27:09Z","timestamp":1678782429000},"source":"Crossref","is-referenced-by-count":30,"title":["Accurate and efficient protein sequence design through learning concise local environment of residues"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7704-9601","authenticated-orcid":false,"given":"Bin","family":"Huang","sequence":"first","affiliation":[{"name":"Key Lab of Intelligent Information Processing, SKLP, Institute of Computing Technology, Chinese Academy of Sciences , Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwen","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Lab of Microbial Physiological & Metabolic Engineering, State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Big Data-based Precision Medicine, School of Engineering Medicine, Beihang University , Beijing 100083, China"},{"name":"Key Laboratory of Big Data-based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People\u2019s Republic of China , Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haicang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Lab of Intelligent Information Processing, SKLP, Institute of Computing Technology, Chinese Academy of Sciences , Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"},{"name":"Zhongke Big Data Academy , Zhengzhou, Henan 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungong","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Lab of Intelligent Information Processing, SKLP, Institute of Computing Technology, Chinese Academy of Sciences , Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"},{"name":"Zhongke Big Data Academy , Zhengzhou, Henan 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Nie","sequence":"additional","affiliation":[{"name":"Key Lab of Microbial Physiological & Metabolic Engineering, State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"School of Life Sciences, Hebei University , Baoding, Hebei 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangshuo","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Lab of Microbial Physiological & Metabolic Engineering, State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"School of Life Sciences, Hebei University , Baoding, Hebei 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Mou","family":"Zheng","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"},{"name":"Institute of Theoretical Physics, Chinese Academy of Sciences , Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Han","sequence":"additional","affiliation":[{"name":"Key Lab of Microbial Physiological & Metabolic Engineering, State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-3134","authenticated-orcid":false,"given":"Zheng","family":"Fan","sequence":"additional","affiliation":[{"name":"Institutional Center for Shared Technologies and Facilities, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-3720","authenticated-orcid":false,"given":"Shiwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Lab of Intelligent Information Processing, SKLP, Institute of Computing Technology, Chinese Academy of Sciences , Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"},{"name":"Zhongke Big Data Academy , Zhengzhou, Henan 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Ye","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Big Data-based Precision Medicine, School of Engineering Medicine, Beihang University , Beijing 100083, China"},{"name":"Key Laboratory of Big Data-based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People\u2019s Republic of China , Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyi","family":"Yang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"},{"name":"Key Lab of Microbial Physiological & Metabolic Engineering, State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-4238","authenticated-orcid":false,"given":"Dongbo","family":"Bu","sequence":"additional","affiliation":[{"name":"Key Lab of Intelligent Information Processing, SKLP, Institute of Computing Technology, Chinese Academy of Sciences , Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100110, China"},{"name":"Zhongke Big Data Academy , Zhengzhou, Henan 450046, 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